RT info:eu-repo/semantics/article
T1 Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response
A1 Requena, Silvia
A1 Treviño, Ana
A1 Cabezas, Teresa
A1 Garcia Delgado, Rosa
A1 Amengual, María José
A1 Lozano, Ana Belén
A1 Peñaranda, María
A1 Fernández, Juan Manuel
A1 Soriano, Vicente
A1 Mendoza, Carmen de
A1 Eiros Bouza, José María
K1 VIH
K1 Mutación
K1 Raltegravir
K1 Dolutegravir
K1 32 Ciencias Médicas
AB Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir.Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded.Results: From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R.Conclusions: A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.
PB Oxford University Press
SN 0305-7453
YR 2017
FD 2017
LK http://uvadoc.uva.es/handle/10324/45360
UL http://uvadoc.uva.es/handle/10324/45360
LA eng
NO Journal of Antimicrobial Chemotherapy,2017, vol. 72, n. 7, p. 2083-2088
NO Producción Científica
DS UVaDOC
RD 12-sep-2024